OVERALL?PROJECT SUMMARY This Wisconsin Alzheimer's Disease Research Center (ADRC) supports cutting-edge and innovative research on the etiology, pathogenesis, diagnosis and treatment of Alzheimer's disease (AD) and related illnesses by establishing a stimulating, interdisciplinary environment for collaborative research and by providing invaluable clinical and postmortem data and ante-mortem biospecimens. This proposal is to add advanced molecular imaging to the Center for tau and amyloid positron emission tomography (PET). The Wisconsin ADRC supports seven well-integrated Cores, including a Neuroimaging Core which will oversee the implementation, management and analysis of valuable new PET data from 300 ADRC participants. The Neuroimaging core is fully integrated with the other cores to support a full-spectrum of timely, innovative research including studies that will: 1) target antecedent biomarkers of preclinical stages of AD, 2) investigate the neurobiology of AD, 3) identify novel vascular and genetic risk factors and linking them to the disease pathology and clinical phenotype, 4) incorporate contemporary biochemical and molecular techniques into clinical-pathologic cohort studies, including genomics, epigenomics, proteomics and next generation genetic sequencing and 5) participate in national dementia research initiatives. The overall goals of the Wisconsin ADRC and its cores are enhanced by the proposed molecular imaging additions: The Administrative Core provides scientific leadership to the ADRC as a whole and will oversee sharing of data. The Clinical Core performs standardized UDS evaluations and will now have critical biomarker images to support its consensus diagnoses. The Outreach, Recruitment and Education (ORE) and the Minority Recruitment Satellite Program (MRSP) Cores will identify participants including underrepresented minorities to participate in this supplemental program. The Data Management and Statistical Core will assist in managing and analyzing the imaging data and derived values. The Neuropathology Core will advise on staging systems for the new images and conduct autopsy evaluations on subjects with ante-mortem molecular imaging. The ORE Core will provide a wide-range of educational and outreach programs regarding the importance of participation in brain donation and ante- mortem imaging, to recruit research volunteers, especially those of color into the proposed addition and Clinical Core. The MRSP Core will work closely with the ORE and Clinical Cores to enhance recruitment and retention of minority participants into the ADRC and into the proposed supplemental PET imaging. The Neuroimaging Core will conduct tau and amyloid PET imaging in addition to its existing cutting edge MRI protocols, will create centiloid maps for convenient interpretation, and will share the images. Findings from these studies will result in powerful investigations on early pathogenesis, identification and treatment for AD that will significantly reduce the human suffering and socio-economic devastations of the disease.